Search Results

You are looking at 1 - 6 of 6 items for

  • Author: Julieta Aisemberg x
  • Refine by access: All content x
Clear All Modify Search
Julieta Aisemberg Centro de Estudios Farmacológicos y Botánicos (CEFYBO, CONICET‐UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

Search for other papers by Julieta Aisemberg in
Google Scholar
PubMed
Close
,
María V Bariani Centro de Estudios Farmacológicos y Botánicos (CEFYBO, CONICET‐UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

Search for other papers by María V Bariani in
Google Scholar
PubMed
Close
,
Claudia A Vercelli Centro de Estudios Farmacológicos y Botánicos (CEFYBO, CONICET‐UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

Search for other papers by Claudia A Vercelli in
Google Scholar
PubMed
Close
,
Manuel L Wolfson Centro de Estudios Farmacológicos y Botánicos (CEFYBO, CONICET‐UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

Search for other papers by Manuel L Wolfson in
Google Scholar
PubMed
Close
, and
Ana M Franchi Centro de Estudios Farmacológicos y Botánicos (CEFYBO, CONICET‐UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

Search for other papers by Ana M Franchi in
Google Scholar
PubMed
Close

The initial inactivation of prostaglandins (PGs) is mediated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). PGs are potent mediators of several biological processes, including inflammation and reproduction. In uterus, PGs play a key role in infection-induced pregnancy loss, in which concentration of this mediator increased. This process is accompanied with the induction of nitric oxide synthase expression and a marked increase in uterine levels of nitric oxide. There is no information concerning nitric oxide contribution to potential changes in PG catabolism, but experimental evidence suggests that nitric oxide modulates PG pathways. The specific objectives of the study were to evaluate the protein expression of HPGD (15-PGDH) and to characterize the nitric oxide-dependent regulation of this enzyme in a model of lipopolysaccharide (LPS)-induced embryonic resorption. Results show that LPS decreased HPGD protein expression and augmented PGE synthase activity; therefore, PGE2 levels increased in uterus in this inflammatory condition. Just as LPS, the treatment with a nitric oxide donor diminished HPGD protein expression in uterine tissue. In contrast, the inhibition of nitric oxide synthesis both in control and in LPS-treated mice increased 15-PGDH levels. Also, we have found that this enzyme and PGE2 levels are not modulated by peroxynitrite, an oxidant agent derived from nitric oxide. This study suggests that LPS and nitric oxide promote a decrease in the ability of the uterus for PG catabolism during bacterially triggered pregnancy loss in mice.

Free access
Fernando Correa Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine

Search for other papers by Fernando Correa in
Google Scholar
PubMed
Close
,
Manuel L Wolfson Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine

Search for other papers by Manuel L Wolfson in
Google Scholar
PubMed
Close
,
Paula Valchi Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine

Search for other papers by Paula Valchi in
Google Scholar
PubMed
Close
,
Julieta Aisemberg Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine

Search for other papers by Julieta Aisemberg in
Google Scholar
PubMed
Close
, and
Ana María Franchi Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine

Search for other papers by Ana María Franchi in
Google Scholar
PubMed
Close

The endocannabinoid system (eCS), is a complex system, comprising the main endogenous ligands anandamide and 2-arachidonoyl glycerol, the cannabinoid receptors CB1 and CB2 and the biosynthetic and degrading enzymes. Cumulative evidence shows that the eCS plays an important role in reproduction, from egg fertilization to parturition. Therefore, alterations in this system, either by recreation/therapeutic use of cannabis or deregulation of the endogenous cannabinoids, might lead to adverse pregnancy outcomes, including retardation in embryo development, poor blastocyst implantation, inhibition of decidualization, miscarriage and compromised placentation. Nevertheless, the molecular mechanisms by which the eCS participates in different stages of pregnancy remain poorly understood. In this review, we will examine the evidence from animal and human studies to support the role of the eCS in implantation, early-to-late pregnancy and placentation as well as the difficulties of targeting this system for treatment of female infertility.

Free access
Julieta Aylen Schander Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, CONICET-UBA, Buenos Aires, Argentina

Search for other papers by Julieta Aylen Schander in
Google Scholar
PubMed
Close
,
Julieta Aisemberg Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, CONICET-UBA, Buenos Aires, Argentina

Search for other papers by Julieta Aisemberg in
Google Scholar
PubMed
Close
,
Fernando Correa Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, CONICET-UBA, Buenos Aires, Argentina

Search for other papers by Fernando Correa in
Google Scholar
PubMed
Close
,
Manuel Luis Wolfson Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, CONICET-UBA, Buenos Aires, Argentina

Search for other papers by Manuel Luis Wolfson in
Google Scholar
PubMed
Close
,
Lorena Juriol Laboratorio de Inmunología de la Reproducción, Centro de Estudios Farmacológicos y Botánicos, CONICET-UBA, Buenos Aires, Argentina

Search for other papers by Lorena Juriol in
Google Scholar
PubMed
Close
,
Cora Cymeryng Laboratorio de Endocrinología Molecular, Centro de Estudios Farmacológicos y Botánicos, CONICET-UBA, Buenos Aires, Argentina

Search for other papers by Cora Cymeryng in
Google Scholar
PubMed
Close
,
Federico Jensen Laboratorio de Inmunología de la Reproducción, Centro de Estudios Farmacológicos y Botánicos, CONICET-UBA, Buenos Aires, Argentina

Search for other papers by Federico Jensen in
Google Scholar
PubMed
Close
, and
Ana María Franchi Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, CONICET-UBA, Buenos Aires, Argentina

Search for other papers by Ana María Franchi in
Google Scholar
PubMed
Close

Maternal lifestyle affects both mother health and pregnancy outcome in humans. Several studies have demonstrated that interventions oriented toward reducing stress and anxiety have positive effects on pregnancy complications such as preeclampsia, excessive gestational weight, gestational diabetes and preterm birth. In this work, we showed that the environmental enrichment (EE), defined as a noninvasive and biologically significant stimulus of the sensory pathway combined with voluntary physical activity, prevented preterm birth (PTB) rate by 40% in an inflammatory mouse model induced by the systemic administration of bacterial lipopolysaccharide (LPS). Furthermore, we found that EE modulates maternal metabolism and produces an anti-inflammatory environment that contributes to pregnancy maintenance. In pregnant mice uterus, EE reduces the expression of TLR4 and CD14 (the LPS receptor and its coactivator protein), preventing the LPS-induced increase in PGE2 and PGF2α release and nitric oxide synthase (NOS) activity. In cervical tissue, EE inhibits cervical ripening events, such as PGE2 release, matrix metalloproteinase (MMP)-9 increased activity and neutrophil recruitment, therefore conserving cervical function. It seems that EE exposure could mimic the stress and anxiety-reducing techniques mentioned above, explaining, at least partially, the beneficial effects of having a healthy lifestyle before and during gestation. Furthermore, we propose that designing an EE protocol for humans could be a noninvasive and preventive therapy for pregnancy complications, averting pre-term birth occurrence and dreaded sequelae that are present in the offspring born too soon.

Restricted access
Carolina Marvaldi Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

Search for other papers by Carolina Marvaldi in
Google Scholar
PubMed
Close
,
Felisa Herrero Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

Search for other papers by Felisa Herrero in
Google Scholar
PubMed
Close
,
Clare Johnson Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA

Search for other papers by Clare Johnson in
Google Scholar
PubMed
Close
,
Julieta Aylen Schander Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

Search for other papers by Julieta Aylen Schander in
Google Scholar
PubMed
Close
,
Fernando Correa Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

Search for other papers by Fernando Correa in
Google Scholar
PubMed
Close
,
Maximiliano Cella Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

Search for other papers by Maximiliano Cella in
Google Scholar
PubMed
Close
,
Julieta Aisemberg Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

Search for other papers by Julieta Aisemberg in
Google Scholar
PubMed
Close
,
Ana María Franchi Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

Search for other papers by Ana María Franchi in
Google Scholar
PubMed
Close
,
Heather Bradshaw Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, USA

Search for other papers by Heather Bradshaw in
Google Scholar
PubMed
Close
, and
Manuel Luis Wolfson Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires-Consejo Nacional de Investigaciones en Ciencia y Técnica, Ciudad Autónoma de Buenos Aires, Argentina

Search for other papers by Manuel Luis Wolfson in
Google Scholar
PubMed
Close

In brief

The cervix plays a crucial role not only in the maintenance of pregnancy but also during delivery, when it undergoes extensive changes. This study highlights the involvement of the endocannabinoidome in cervical remodeling, emphasizing its relevance in the shift from a nonpregnant to pregnant state and its potential contribution to preterm delivery in inflammatory contexts.

Abstract

During pregnancy, the main role of the cervix is to isolate the fetus from outside pathogens and maintain the relatively closed system of uterine gestation. Conversely, toward the end of pregnancy, the cervix must be remodeled to increase flexibility and allow the delivery. This process is called cervical remodeling and dysregulation of the process plays a role in premature delivery. The endocannabinoidome plays an important role in several reproductive events; however, its function on cervical tissue throughout pregnancy is poorly understood. The goal of this study was to evaluate the presence and participation of the endocannabinoidome in lipopolysaccharide (LPS)-induced cervical changes. Therefore, we evaluated key components of the endocannabinoidome in cervical tissue from nonpregnant mice and pregnant mice with and without LPS treatment. Using mass spectrometric analysis, we found an increase in anandamide and 2-arachidonoylglycerol in the cervix of pregnant mice when compared to nonpregnant mice. We have also found a reduction in FAAH protein expression in these tissues. Furthermore, when treated with LPS, we observed a reduction in the cervical immunostaining with anti-CB1 and anti-CB2 antibodies. Likewise, using cervix explants from pregnant mice, we found that LPS significantly increased cervical metalloprotease activity and cyclooxygenase 2, which were subsequently modulated by cannabinoid receptor antagonists. Collectively, our findings suggest that an LPS-induced imbalance of cervix endocannabinoidome likely contributes to premature cervical remodeling, which is part of the key components that contribute to premature delivery.

Restricted access
María Victoria Bariani
Search for other papers by María Victoria Bariani in
Google Scholar
PubMed
Close
,
Ana Paula Domínguez Rubio
Search for other papers by Ana Paula Domínguez Rubio in
Google Scholar
PubMed
Close
,
Maximiliano Cella
Search for other papers by Maximiliano Cella in
Google Scholar
PubMed
Close
,
Juliana Burdet Laboratory of Physiopathology of Pregnancy and Labor, Laboratory of Physiopathogeny, Center for Pharmacological and Botanical Studies, National Research Council, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina and

Search for other papers by Juliana Burdet in
Google Scholar
PubMed
Close
,
Ana María Franchi
Search for other papers by Ana María Franchi in
Google Scholar
PubMed
Close
, and
Julieta Aisemberg
Search for other papers by Julieta Aisemberg in
Google Scholar
PubMed
Close

Prematurity is the leading cause of perinatal morbidity and mortality worldwide. There is a strong causal relationship between infection and preterm births. Intrauterine infection elicits an immune response involving the release of inflammatory mediators like cytokines and prostaglandins (PG) that trigger uterine contractions and parturition events. Anandamide (AEA) is an endogenous ligand for the cannabinoid receptors CB1 and CB2. Similarly to PG, endocannabinoids are implicated in different aspects of reproduction, such as maintenance of pregnancy and parturition. Little is known about the involvement of endocannabinoids on the onset of labor in an infectious milieu. Here, using a mouse model of preterm labor induced by lipopolysaccharide (LPS), we explored changes on the expression of components of endocannabinoid system (ECS). We have also determined whether AEA and CB antagonists alter PG production that induces labor. We observed an increase in uterine N-acylphosphatidylethanolamine-specific phospholipase D expression (NAPE-PLD, the enzyme that synthesizes AEA) upon LPS treatment. Activity of catabolic enzyme fatty acid amide hydrolase (FAAH) did not change significantly. In addition, we also found that LPS modulated uterine cannabinoid receptors expression by downregulating Cb2 mRNA levels and upregulating CB1 protein expression. Furthermore, LPS and AEA induced PGF2a augmentation, and this was reversed by antagonizing CB1 receptor. Collectively, our results suggest that ECS may be involved in the mechanism by which infection causes preterm birth.

Free access
Valeria Roca Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina and Academia Nacional de Medicina, Buenos Aires, Argentina

Search for other papers by Valeria Roca in
Google Scholar
PubMed
Close
,
Luciana Larocca Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina and Academia Nacional de Medicina, Buenos Aires, Argentina

Search for other papers by Luciana Larocca in
Google Scholar
PubMed
Close
,
Mario Calafat Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina and Academia Nacional de Medicina, Buenos Aires, Argentina

Search for other papers by Mario Calafat in
Google Scholar
PubMed
Close
,
Julieta Aisemberg Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina and Academia Nacional de Medicina, Buenos Aires, Argentina

Search for other papers by Julieta Aisemberg in
Google Scholar
PubMed
Close
,
Roberto Meiss Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina and Academia Nacional de Medicina, Buenos Aires, Argentina

Search for other papers by Roberto Meiss in
Google Scholar
PubMed
Close
,
Ana M Franchi Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina and Academia Nacional de Medicina, Buenos Aires, Argentina

Search for other papers by Ana M Franchi in
Google Scholar
PubMed
Close
, and
Claudia Pérez Leirós Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina and Academia Nacional de Medicina, Buenos Aires, Argentina

Search for other papers by Claudia Pérez Leirós in
Google Scholar
PubMed
Close

A functional interaction between progesterone, Th2 cytokines and a suitable balance between nitric oxide and prostaglandins in the uterus is considered to have a major role in the success of embryo implantation and pregnancy. Non-obese diabetic (NOD) mice offer a suitable model to study the modulatory role of Th1 cytokines on uterus signalling and function, since at the prediabetic stage they develop a spontaneous Th1 autoimmune response against exocrine glands similar to Sjögren’s syndrome. Vasoactive intestinal peptide (VIP) is a vasoactive neuro- and immunopeptide that promotes Th2 profiles and contributes to the smooth muscle relaxation and vasodilation. The aim of the present study was to investigate the activities of nitric oxide synthase and cyclo-oxygenase and the effect of VIP in the uterus of NOD mice with an emerging Th1 cytokine response. We present evidence of a reduced basal and VIP-stimulated activity of both enzymes in the uterus of NOD mice compared with normal BALB/c mice in proestrus. An altered functional interaction between both enzymes is also present in NOD mice at the time when increased levels of serum interleukin (IL)-12 and tumour necrosis factor-α but not interferon (IFN)-γ or IL-10 were detected. We conclude that signalling alterations in uteri of NOD mice are simultaneous to the onset of a systemic Th1 cytokine response.

Free access